1. Technical Field of the Invention
The present invention relates to the formulation of glycols into cosmetic compositions comprising a substantially alcohol-free aqueous phase, to solubilize therein effective amounts of melatonin or analog thereof.
The present invention also relates to novel alcohol-free aqueous cosmetic compositions comprising melatonin or analog thereof and a solubilizing amount of at least one glycol.
2. Description of the Prior Art
Melatonin, or N-acetyl-5-methoxytryptamine, known especially for its bioactivity on the circadian rhythm regulating hormone production, is also known for its antioxidizing activity (Reiter R. J., Verhandung der Deutschen Zoologischen Gesellschaft, 87 (2), 195-204 (1994); Reiter R. J. et al., Neuroendocrinol Letter, 15 (1-3), 103-113 (1993); Reiter R. J. et al., J. Pineal Res., 18 (1), 1-11 (1995), in particular its antiradical activity (Reiter R. J. et al., Brazilian Journal of Medical and Biological Research, 26 (22), 1141-1155 (1993)). The majority of studies on the antioxidant properties of melatonin are concerned with oxidation phenomena related to aging of the brain (Pooggeler B. et al., J. Pineal Res., 14 (4), 151-168 (1993); Cagnoli C. M. et al., J. Pineal Res., 18 (4), 222-226 (1995); Melchiorri D. et al., FASEB J., 9 (12), 1205-1210 (1995); Sewerynek E. et al., Neuroscience Letters, 195 (3), 203-205 (1995)).
Melatonin has also been described for formulation into dermocosmetics for improving the appearance of skin (JP-61/221,104; WO-86/05,093) or for protecting the skin against the deleterious effects of UV radiation (EP-0,438,856; E. Bangha et al., Dermatology, 191 , 2!, 176 (1995)). It is recommended to employ melatonin at concentrations of between 10.sup.-4 % and 10% by weight with respect to the total weight of the composition.
Thus, WO-86/05,093 describes a cosmetic composition comprising melatonin for increasing the sensitivity of the skin to estrogens, in particular for the treatment of acne or the prevention of hair loss. The amounts of melatonin recommended in this application are generally between 10.sup.-4 and more than 1% by weight with respect to the total weight of the composition.
Similarly, EP-438,856, relating to compositions for protecting the skin against the damaging effects of UV radiation, recommends amounts of melatonin of between 1% and 10% by weight for topical compositions, the only example of this type of composition being an anhydrous ointment comprising 10% of melatonin.
In order for melatonin applied topically to have satisfactory effectiveness, it is essential that it be well dissolved in the vehicle therefor. It has been determined that melatonin, at the doses heretofore recommended, is soluble neither in water nor in the oils formulated into cosmetics. Thus, melatonin is insoluble at 1% by weight in water, mineral oils (liquid petrolatum), fatty esters (2-ethylhexyl palmitate, dodecyl benzoate, 2-octyldodecyl neopentanoate), fatty alcohol ethers (polyoxypropylenated myristyl alcohol, polyoxypropylenated stearyl alcohol, 2-ethylhexyl glyceryl ether palmitate) or fatty alcohols (octyldodecanol, isostearyl alcohol, 2-hexyl-1-decyl alcohol).
To properly dissolve melatonin or analogs thereof in fluid compositions, such as creams, gels or lotions, it is necessary to include ethanol.
Thus, WO-86/05,093 recommends employing between 10% and 30% by weight of ethanol.
Likewise, JP-61/221,104 describes different solutions comprising between 10.sup.-4 % and 0.01% by weight of melatonin and between 3% and 8% by weight of ethanol, the melatonin/ethanol ratio by weight being between 1/30,000 and 1/500.
Too, EP-578,620 describes different compositions in the form of gels comprising between 5% and 30% of ethanol, the melatonin/alcohol ratio being between 1/450 and 1/10.
Indeed, for compositions as described in WO-86/05,093, it is necessary to incorporate more than 35% by weight of ethanol in order to obtain a stable recrystallization-free composition containing 0.5% by weight of melatonin. The greater the amount of melatonin or analog thereof in the composition, the greater the amount of alcohol required to provide a stable composition.
Including such amounts of alcohol is inappropriate for the formulation of cosmetic compositions, since alcohols cause drying of the skin and the phenomena of irritation, warming and red blotches. While such phenomena may be accepted for pharmaceutical compositions, where a balance is sought between the beneficial effect of the active agent or principle (in this case melatonin) and its side effects and/or those of the composition, this is not the case for cosmetic compositions, which have to be free of any undesirable side effect unacceptable to the user.